Sequentially cross-linked polyethylene

ABSTRACT

A method of producing an improved polyethylene, especially an ultra-high molecular weight polyethylene utilizes a sequential irradiation and annealing process to form a highly cross-linked polyethylene material. The use of sequential irradiation followed by sequential annealing after each irradiation allows each dose of irradiation in the series of doses to be relatively low while achieving a total dose which is sufficiently high to cross-link the material. The process may either be applied to a preformed material such as a rod or bar or sheet made from polyethylene resin or may be applied to a finished polyethylene part. If applied to a finished polyethylene part, the irradiation and annealing must be accomplished with the polyethylene material not in contact with oxygen at a concentration greater than 1% oxygen volume by volume. When applied to a preform, such as a rod, the annealing of the bulk polymer part of the rod from which the finished part is made must take place on the rod before the implant is machined therefrom and exposed to oxygen.

CROSS-REFERENCED TO RELATED APPLICATIONS

[0001] This application is based on U.S. Provisional Application No.60/386,660 filed on Jun. 6, 2002, the teachings of which areincorporated herein by reference.

BACKGROUND OF THE INVENTION

[0002] This invention relates to medical implants formed of a polymericmaterial such as ultra-high molecular weight polyethylene, with superioroxidation and wear resistance produced by a sequential irradiation andannealing process.

[0003] Various polymer systems have been used for the preparation ofartificial prostheses for biomedical use, particularly orthopedicapplications. Among them, ultra-high molecular weight polyethylene iswidely used for articulation surfaces in artificial knee, hip, and otherjoint replacements. Ultra-high molecular weight polyethylene (UHMWPE)has been defined as those linear polyethylenes which have a relativeviscosity of 2.3 or greater at a solution concentration of 0.05% at 135°C. in decahydronaphthalene. The nominal weight—average molecular weightis at least 400,000 and up to 10,000,000 and usually from three to sixmillion. The manufacturing process begins with the polymer beingsupplied as fine powder which is consolidated into various forms, suchas rods and slabs, using ram extrusion or compression molding.Afterwards, the consolidated rods or slabs are machined into the finalshape of the orthopedic implant components. Alternatively, the componentcan be produced by compression molding of the UHMWPE resin powder.

[0004] All components must then go through a sterilization procedureprior to use, but usually after being packaged. There exists severalsterilization methods which can be utilized for medical applications,such as the use of ethylene oxide, gas plasma, heat, or radiation.However, applying heat to a packaged polymeric medical product candestroy either the integrity of the packaging material (particularly theseal, which prevents bacteria from going into the package after thesterilization step) or the product itself.

[0005] It has been recognized that regardless of the radiation type, thehigh energy beam causes generation of free radicals in polymers duringradiation. It has also been recognized that the amount or number of freeradicals generated is dependent upon the radiation dose received by thepolymers and that the distribution of free radicals in the polymericimplant depends upon the geometry of the component, the type of polymer,the dose rate, and the type of radiation beam. The generation of freeradicals can be described by the following reaction (which usespolyolefin and gamma ray irradiation for illustration):

[0006] gamma rays

Polyolefin ---------------- r. where r. are primary free radicals *  (1)

[0007] *(through C-C chain scission or C-H scission)

[0008] Depending on whether or not oxygen is present, primary freeradicals r. will react with oxygen and the polymer according to thefollowing reactions as described in “Radiation Effects on Polymers,”edited by Roger L. Clough and Shalaby W. Shalaby, published by AmericanChemical Society, Washington, D.C., 1991.

[0009] In the presence of oxygen

O₂ r.-----------rO₂  (2)

rO₂+polyolefin -------rOOH+P  (3)

P.+O₀ ---------------- P0₂.  (4)

O₂ P0₂.+polyolefin ---- POOH+P.--------P0₂.  (5)

rO₂., P0₂.------ Some chain scission products room temperature  (6)

rOOH, POOH -------------- free radicals, rOH, POH  (7)

P.+P0₂ ------POOP (ester cross-links)  (8)

2 P.------------P-P (C-C cross-links)  (9)

[0010] In radiation in air, primary free radicals r. will react withoxygen to form peroxyl free radicals r0₂., which then react withpolyolefin (such as UHMWPE) to start the oxidative chain scissionreactions (reactions 2 through 6). Through these reactions, materialproperties of the plastic, such as molecular weight, tensile and wearproperties, are degraded.

[0011] It has been found that the hydroperoxides (rOOH and POOH) formedin reactions 3 and 5 will slowly break down as shown in reaction 7 toinitiate post-radiation degradation. Reactions 8 and 9 representtermination steps of free radicals to form ester or carbon-carboncross-links. Depending on the type of polymer, the extent of reactions 8and 9 in relation to reactions 2 through 7 may vary. For irradiatedUHMWPE, a value of 0.3 for the ratio of chain scission to cross-linkinghas been obtained, indicating that even though cross-linking is adominant mechanism, a significant amount of chain scission occurs inirradiated polyethylene.

[0012] By applying radiation in an inert atmosphere, since there is nooxidant present, the primary free radicals r. or secondary free radicalsP. can only react with other neighboring free radicals to formcarbon-carbon cross-links, according to reactions 10 through 12 below.If all the free radicals react through reactions 10 through 12, therewill be no chain scission and there will be no molecular weightdegradation. Furthermore, the extent of cross-linking is increased overthe original polymer prior to irradiation. On the other hand, if not allthe free radicals formed are combined through reactions 10, 11 and 12,then some free radicals will remain in the plastic component.

[0013] In an Inert Atmosphere

r.+polyolefin ----------- P.  (10)

2 r. ---------- r-r (C-C cross-linking)  (11)

2 P. ---------- P-P (C-C cross-linking)  (12)

[0014] It is recognized that the fewer the free radicals, the better thepolymer retains its physical properties over time. The greater thenumber of free radicals, the greater the degree of molecular weight andpolymer property degradation will occur. Applicant has discovered thatthe extent of completion of free radical cross-linking reactions isdependent on the reaction rates and the time period given for reactionto occur.

[0015] UHMWPE is commonly used to make prosthetic joints such asartificial hip joints. In recent years, it has been found that tissuenecrosis and interface osteolysis may occur in response to UHMWPE weardebris. For example, wear of acetabular cups of UHMWPE in artificial hipjoints may introduce microscopic wear particles into the surroundingtissues.

[0016] Improving the wear resistance of the UHMWPE socket and, thereby,reducing the rate of production of wear debris may extend the usefullife of artificial joints and permit them to be used successfully inyounger patients. Consequently, numerous modifications in physicalproperties of UHMWPE have been proposed to improve its wear resistance.

[0017] It is known in the art that ultrahigh molecular weightpolyethylene (UHMWPE) can be cross-linked by irradiation with highenergy radiation, for example gamma radiation, in an inert atmosphere orvacuum. Exposure of UHMWPE to gamma irradiation induces a number offree-radical reactions in the polymer. One of these is cross-linking.This cross-linking creates a 3-dimensional network in the polymer whichrenders it more resistant to adhesive wear in multiple directions. Thefree radicals formed upon irradiation of UHMWPE can also participate inoxidation which reduces the molecular weight of the polymer via chainscission, leading to degradation of physical properties, embrittlementand a significant increase in wear rate. The free radicals are verylong-lived (greater than eight years), so that oxidation continues overa very long period of time resulting in an increase in the wear rate asa result of oxidation over the life of the implant.

[0018] Sun et al. U.S. Pat. No. 5,414,049, the teachings of which areincorporated herein by reference, broadly discloses the use of radiationto form free radicals and heat to form cross-links between the freeradicals prior to oxidation.

[0019] Hyun et al. U.S. Pat. No. 6,168,626 relates to a process forforming oriented UHMWPE materials for use in artificial joints byirradiating with low doses of high-energy radiation in an inert gas orvacuum to cross-link the material to a low degree, heating theirradiated material to a temperature at which compressive deformation ispossible, preferably to a temperature near the melting point or higher,and performing compressive deformation followed by cooling andsolidifying the material. The oriented UHMWPE materials have improvedwear resistance. Medical implants may be machined from the orientedmaterials or molded directly during the compressive deformation step.The anisotropic nature of the oriented materials may render themsusceptible to deformation after machining into implants.

[0020] Salovey et al. U.S. Pat. No. 6,228,900, the teachings of whichare incorporated by reference, relates to a method for enhancing thewear-resistance of polymers, including UHMWPE, by cross-linking them viairradiation in the melt.

[0021] Saum et al. U.S. Pat. No. 6,316,158 relates to a process fortreating UHMWPE using irradiation followed by thermally treating thepolyethylene at a temperature greater than 150° C. to recombinecross-links and eliminate free radicals.

[0022] Several other prior art patents attempt to provide methods whichenhance UHMWPE physical properties. European Patent Application 0 177522 81 relates to UHMWPE powders being heated and compressed into ahomogeneously melted crystallized morphology with no grain memory of theUHMWPE powder particles and with enhanced modulus and strength. U.S.Pat. No. 5,037,928 relates to a prescribed heating and cooling processfor preparing a UHMWPE exhibiting a combination of properties includinga creep resistance of less than 1% (under exposure to a temperature of23° C. and a relative humidity of 50% for 24 hours under a compressionof 1000 psi) without sacrificing tensile and flexural properties. U.K.Patent Application GB 2 180 815 A relates to a packaging method where amedical device which is sealed in a sterile bag, afterradiation/sterilization, is hermetically sealed in a wrapping member ofoxygen-impermeable material together with a deoxidizing agent forprevention of post-irradiation oxidation.

[0023] U.S. Pat. No. 5,153,039 relates to a high density polyethylenearticle with oxygen barrier properties. U.S. Pat. No. 5,160,464 relatesto a vacuum polymer irradiation process.

SUMMARY OF THE INVENTION

[0024] The present invention relates to a method for providing apolymeric material, such as UHMWPE, with superior oxidation resistance,mechanical strength and wear properties. For the purpose ofillustration, UHMWPE will be used as an example to describe theinvention. However, all the theories and processes described hereaftershould also apply to other polymeric materials such as polypropylene,high density polyethylene, polyhydrocarbons, polyester, nylon,polyurethane, polycarbonates and poly(methylmethcrylate) unlessotherwise stated. The method involves using a series of relatively lowdoses of radiation with an annealing process after each dose.

[0025] As stated above, UHMWPE polymer is very stable and has very goodresistance to aggressive media except for strong oxidizing acids. Uponirradiation, free radicals are formed which cause UHMWPE to becomeactivated for chemical reactions and physical changes. Possible chemicalreactions include reacting with oxygen, water, body fluids, and otherchemical compounds while physical changes include density,crystallinity, color, and other physical properties. In the presentinvention, the sequential radiation and annealing process greatlyimproves the physical properties of UHMWPE when compared to applying thesame total radiation dose in one step. Furthermore, this process doesnot employ stabilizers, antioxidants, or any other chemical compoundswhich may have potentially adverse effects in biomedical or orthopedicapplications.

[0026] It is also known that at relatively low dose levels (<5 MRads) ofirradiation residual free radicals are mostly trapped in the crystallineregion while most free radicals crosslink in the amorphous region. Thereis a steep free radical concentration gradient across thecrystalline-amorphous boundary, which provides a significant drivingforce for free radicals to diffuse into the amorphous region where theycan crosslink upon subsequent annealing. However, if the polyethylene isallowed to continuously accumulate higher radiation doses withoutinterruptive annealing, molecules in the amorphous region become moreand more stiffened due to increased crosslinking. As a result, theamorphous region traps more and more free radicals. This leads to adiminished free radical gradient across the crystalline-amorphousboundary, thereby reducing the driving force for free radical diffusionupon subsequent annealing. By limiting the incremental dose to below 5MRads and preferably below 3.5 MRads and following with annealing, arelatively higher free radical diffusion driving force can bemaintained, allowing a more efficient free radical reduction uponannealing. If higher radiation doses are used, there could becross-linking at the chain folded crystal surfaces. This could hamperthe movement of free radicals from the crystal to the amorphous regions.

[0027] It has been found that polyethylene crystallinity increasescontinuously with increasing radiation-doses due to chain-scission(approximately 55% before radiation, increasing to 60% at 3.0 MRads, andto 65% at 10 MRads).

[0028] As the crystallinity increases with increasing dose of radiation,more residual free radicals are created and stored in the extracrystalline regions, which makes it increasingly more difficult toeliminate free radicals by annealing below the melt temperature.However, treating above the melting temperature (re-melting)significantly alters the crystallinity and crystal morphology whichleads to significant reduction in mechanical properties such as yieldstrength and ultimate tensile strength and creep resistance and theseproperties are important for the structural integrity of the implant.

[0029] An orthopedic preformed material such as a rod, bar orcompression molded sheet for the subsequent production of a medicalimplant such as an acetabular or tibial implant with improved wearresistance is made from a polyethylene material cross-linked at leasttwice by irradiation and thermally treated by annealing after eachirradiation. The material is cross-linked by a total radiation dose offrom about 2 MRads to 100 MRads and preferably between 5 MRads and 10MRads. The incremental dose for each irradiation is between about 2MRads and about 5 MRads. The weight average molecular weight of thematerial is over 400,000.

[0030] The annealing takes place at a temperature greater than 25° C.,preferably between 110° C. and 135° C. but less than the melting point.Generally, the annealing takes place for a time and temperature selectedto be at least equivalent to heating the irradiated material at 50° C.for 144 hours as defined by Arrenhius' equation 14. The material isheated for at least about 4 hours and then cooled to room temperaturefor the subsequent irradiation in the series.

[0031] By limiting the incremental dose to below 5 MRads and preferablybelow 3.5 MRads and following with annealing, the crystallinity willfluctuate between 55% and 60% (instead of 55-65%) and hence both theamount of chain-scission and residual free-radical concentration can besignificantly reduced.

[0032] The polyethylene of the present invention may be in the form of apreformed rod or sheet with a subsequent production of a medical implantwith improved wear resistance. The preformed rod or sheet iscross-linked at least twice by irradiation and thermally treated byannealing after each radiation. The incremental dose for each radiationis preferably between about 2 and 5 MRads with the total dose between 2and 100 MRads and preferably between 5 and 10 MRads.

[0033] After each irradiation, the preformed material is annealed eitherin air or in an inner atmosphere at a temperature of greater than 25° C.and preferably less than 135° C. or the melting point. Preferably, theannealing takes place for a time and temperature selected to be at leastequivalent to heating the irradiated material at 50° C. for 144 hours asdefined by Arrenhius' equation (14). Generally, each heat treatmentlasts for at least 4 hours and preferably about 8 hours.

[0034] The preformed polyethylene material is then machined into amedical implant or other device. If the irradiation process occurred inair, then the entire outer skin to about 2 mm deep is removed from thepreform prior to machining the medical implant or other device. If theprocess was done in a vacuum or an inner atmosphere such a nitrogen,then the outer skin may be retained.

[0035] The end-results of reduced chain-scission and free-radicalconcentration are improved mechanical properties, improved oxidationresistance and enhanced wear resistance.

BRIEF DESCRIPTION OF THE DRAWINGS

[0036]FIG. 1 shows the oxidation index profiles of the specimens ofExample 8; and

[0037]FIG. 2 shows the oxidation index profiles of the specimens ofExample 11.

DETAILED DESCRIPTION

[0038] Abbreviations used in this application are as follows:

[0039] UHMW—ultra-high molecular weight

[0040] UHMWPE—ultra-high molecular weight polyethylene

[0041] HMW—high molecular weight

[0042] HMWPE—high molecular weight polyethylene

[0043] This invention provides a method for improving the wearresistance of a polymer by crosslinking (preferably the bearing surfaceof the polymer) and then thermally treating the polymer, and theresulting polymer. Preferably, the most oxidized surface of the polymeris also removed. Also presented are the methods for using the polymericcompositions for making products and the resulting products, e.g., invivo implants.

[0044] The method of the invention utilizes at least two separateirradiations for crosslinking a polymer followed by a like number ofthermal treatments to decrease the free radicals to produce either atreated fully formed or a preformed polymeric composition. The term“preformed polymeric composition” means that the polymeric compositionis not in a final desired shape or from (i.e., not a final product). Forexample, where the final product of the preformed polymeric compositionis an acetabular cup, the at least two irradiations and thermaltreatments of the polymer could be performed at pre-acetabular cupshape, such as when the preformed polymeric composition is in the formof a solid bar or block. Of course, the process of the present inventioncould be applied to a fully formed implant if the process is done withthe implant in an oxygen reduced atmosphere.

[0045] In the present invention, the wear resistance of a polymer isimproved by crosslinking. The crosslinking can be achieved by variousmethods known in the art, for example, by irradiation from a gammaradiation source or from an electron beam, or by photocrosslinking. Thepreferred method for crosslinking the polymer is by gamma irradiation.The polymer is preferably crosslinked in the form of an extruded bar ormolded block.

[0046] In the preferred method, the crosslinked polymer is subjected tothermal treatment such as by annealing (i.e. heated above at or belowthe melting temperature of the crosslinked polymer) to produce thepreformed polymeric composition.

[0047] In the preferred embodiment of the invention, the outer layer ofthe resulting preformed polymeric composition, which is generally themost oxidized and least crosslinked and, thus, least wear resistant, isremoved. For example, the bearing surface of the preformed polymericcomposition may be fashioned from inside, e.g., by machining away thesurface of the irradiated and thermally treated composition before orduring fashioning into the final product, e.g., into an implant. Bearingsurfaces are surfaces which are in moving contact, e.g., in a sliding,pivoting, or rotating relationship to one another.

[0048] High molecular weight (HMW) and ultra-high molecular weight(UHMW) polymers are preferred, such as HMW polyethylene (HMWPE), UHMWpolyethylene (UHMWPE), and UHMW polypropylene. HMW polymers havemolecular weights ranging from about 10⁵ grams per mole to just below10⁶. UHMW polymers have molecular weights equal to or higher than 10⁶grams per mole, preferably from 10⁶ to about 10⁷. The polymers aregenerally between about 400,000 grams per mole to about 10,000,000 andare preferably polyolefinic materials.

[0049] For implants, the preferred polymers are those that are wearresistant and have exceptional chemical resistance. UHMWPE is the mostpreferred polymer as it is known for these properties and is currentlywidely used to make acetabular cups for total hip prostheses andcomponents of other joint replacements. Examples of UHMWPE are thosehaving molecular weight ranging from about 1 to 8×10⁶ grams per mole,examples of which are: GUR 1150 or 1050 (Hoechst-Celanese Corporation,League City, Tex.) with a weight average molecular weight of 5 to 6×10⁶grams per mole; GUR 1130 with a weight average molecular weight of 3 to4×10⁶; GUR 1120 or 1020 with a weight average molecular weight of 3 to4×10⁶; RCH 1000 (Hoechst-Celanese Corp.) with a weight average ofmolecular weight of 4×10⁶ and HiFax 1900 of 2 to 4×10⁶ (HiMont, Elkton,Md.). Historically, companies which make implants have usedpolyethylenes such as HIFAX 1900, GUR 1020, GUR 1050, GUR 1120 and GUR1150 for making acetabular cups.

[0050] Sterilization Methods: All polymeric products must be sterilizedby a suitable method prior to implanting in the human body. For theformed crosslinked and thermally treated polymeric compositions (i.e.,the final products) of the present invention, it is preferable that theproducts be sterilized by a non-radiation based method, such as ethyleneoxide or gas plasma, in order not to induce additional crosslinking freeradicals and/or oxidation of the previously treated preformed polymericcomposition. Compared to radiation sterilization, a non-radiationsterilization method has a minor effect on the other important physicalcharacteristics of the product.

[0051] The degree of crystallinity can be determined using methods knownin the art, e.g. by differential scanning calorimetry (DSC), which isgenerally used to assess the crystallinity and melting behavior of apolymer. Wang, X. & Salovey, R., J. App. Polymer Sci., 34:593-599(1987).

[0052] Wide-angle X-ray scattering from the resulting polymer can alsobe used to further confirm the degree of crystallinity of the polymer,e.g. as described in Spruiell, J. E., & Clark, E. S., in “Methods ofExperimental-Physics,” L. Marton & C. Marton, Eds., Vol. 16, Part B,Academic Press, New York (1980). Other methods for determining thedegree of crystallinity of the resulting polymer may include FourierTransform Infrared Spectroscopy (FTIR), e.g., as described in “FourierTransform Infrared Spectroscopy And Its Application To PolymericMaterials,” John Wiley and Sons, New York, U.S.A. (1982)} and densitymeasurement (ASTM D1505-68). Measurements of the gel content andswelling are generally used to characterize crosslink distributions inpolymers; the procedure is described in Ding, Z. Y., et al., J. PolymerSci., Polymer Chem., 29:1035-38 (1990). FTIR can also be used to assessthe depth profiles of oxidation as well as other chemical changes suchas unsaturation {Nagy, E. V. & Li, S., “A Fourier transform infraredtechnique for the evaluation of polyethylene orthopedic bearingmaterials,” Trans. Soc. for Biomaterials, 13:109 (1990); Shinde, A. &Salovey, R., J. Polymer Sci., Polm. Phys. Ed., 23:1681-1689 (1985)}.

[0053] Another aspect of the invention presents a process for makingimplants using the preformed polymeric composition of the presentinvention. The preformed polymeric composition may be shaped, e.g.,machined, into the appropriate implants using methods known in the art.Preferably, the shaping process, such as machining, removing theoxidized surface of the composition.

[0054] The preformed polymeric compositions of the present invention canbe used in any situation where a polymer, especially UHMWPE, is calledfor, but especially in situations where high wear resistance is desired.More particularly, these preformed polymeric compositions are useful formaking implants.

[0055] An important aspect of this invention presents implants that aremade with the above preformed polymeric compositions or according to themethods presented herein. In particular, the implants are produced frompreformed polymeric composition made of UHMWPE irradiated andcrosslinked at least twice each time followed by annealing and thenremoving the oxidized surface layer and then fabricating into a finalshape. The preformed polymeric composition of the present invention canbe used to make the acetabular cup, or the insert or liner of the cup,or trunnion bearings (e.g. between the modular head and the hip stem).In the knee joint, the tibial plateau (femoro-tibial articulation), thepatellar button (patello-femoral articulation), and/or other bearingcomponents, depending on the design of the artificial knee joint. Thesewould include application to mobile bearing knees where articulationbetween the tibial insert and tibial tray occurs. In the shoulder, theprocess can be used in the glenoid component. In the ankle joint, thepreformed polymeric composition can be used to make the talar surface(tibiotalar articulation) and other bearing components. In the elbowjoint, the preformed polymeric composition can be used to make theradio-humeral joint, ulno-humeral joint, and other bearing components.In the spine, the preformed polymeric composition can be used to makeintervertebral disk replacement and facet joint replacement. Thepreformed polymeric composition can also be made into temporo-mandibularjoint (jaw) and finger joints. The above are by way of example, and arenot meant to be limiting.

[0056] The following discusses the first and second aspects of theinvention in more detail.

[0057] First Aspect of the Invention: Polymeric Compositions withIncreased Wear Resistance.

[0058] The first aspect of the invention provides preformed polymericcompositions which are wear resistant and useful for making in vivoimplants. In this aspect, for polymers in general, and more preferablyUHMW and HMW polymers, and most preferably UHMWPE and HMWPE, the atleast two (2) incremental irradiation doses are preferably from about 1to about 100 Mrad, and more preferably, from about 2 to about 5 Mrad.This most preferable range is based on achieving a reasonable balancebetween improved wear resistance and minimal degradation of otherimportant physical properties. The total dose is between 2 and 100 MRadand more preferably 5 to about 10 MRads.

[0059] In vivo implants of the present invention, i.e., irradiatedwithin the above dose ranges are expected to function in vivo withoutmechanical failure. The UHMWPE acetabular cups used by Oonishi et al.[in Radiat. Phys. Chem., 39:495-504 (1992)] were irradiated to 100 Mradand functioned in vivo without reported mechanical failure as long as 26years of clinical use. Furthermore, it is surprising that, as shown inthe EXAMPLES, acetabular cups from the preformed polymeric compositionprepared according to the present invention, but irradiated to much lessthan 100 Mrad, exhibited much higher wear resistance than reported byOonishi et al.

[0060] On the other hand, if a user is primarily concerned with reducingwear, and other physical properties are of secondary concern, then ahigher dose than the above stipulated most preferable range (e.g., 5 to10 Mrad) may be appropriate, or vice versa (as illustrated in thedetailed examples in the following section). The optimum radiation doseis preferably based on the total dose received at the level of thebearing surface in the final product. Gamma radiation is preferred.

[0061] The preferred annealing temperature after each sequentialirradiation is below the melting temperature of the UHMWPE which isgenerally below 135° C.

[0062] The annealing temperature is preferably from about roomtemperature to below the melting temperature of the irradiated polymer;more preferably from about 90° C. to about 1° C. below the meltingtemperature of the irradiated polymer; and most preferably from about110° C. to about 130° C. For example, UHMWPE may be annealed at atemperature from about 25° C. to about 140° C., preferably from about50° C. to about 135° C. and more preferably from about 80° C. to about135° C. and most preferably between 110° C. to 130° C. The annealingperiod is preferably from about 2 hours to about 7 days, and morepreferably from about 7 hours to about 5 days and most preferably fromabout 10 hours to about 24 hours.

[0063] Instead of using the above range of radiation dose as acriterion, the appropriate amount of crosslinking may be determinedbased on the degree of swelling, gel content, or molecular weightbetween crosslinks after thermal treatment. This alternative is based onthe applicant's findings (detailed below) that acetabular cups made fromUHMWPE falling within a preferred range of these physical parametershave reduced or non-detectable wear. The ranges of these physicalparameters include one or more of the following: a degree of swelling ofbetween about 1.7 to about 5.3; molecular weight between crosslinks ofbetween about 400 to about 8400 g/mol; and a gel content of betweenabout 95% to about 99%. A preferred polymer or final product has one ormore, and preferably all, of the above characteristics. These parameterscan also be used as starting points in the second aspect of theinvention (as illustrated by the flowchart, discussed below) fordetermining the desired radiation dose to balance the improvement inwear resistance with other desired physical or chemical properties, suchas polymer strength or stiffness.

[0064] After crosslinking and thermal treatment, preferably, the mostoxidized surface of the preformed polymeric composition is removed. Thedepth profiles of oxidation of the preformed polymeric composition canbe determined by methods known in the art, such as FTIR. In general, themost oxidized surface of preformed polymeric composition which isexposed to air is removed, e.g. by machining, before or while fashioningthe preformed polymeric composition into the final product. Since oxygendiffuses through the polyethylene with time, the sequentialirradiation/annealing preferably should be completed prior to oxygendiffusing in high concentrations to the area of the preform from whichthe final part is made.

[0065] As noted above, the most preferable range of total dose forcrosslinking radiation (i.e., from 5 to 10 Mrad) was based on Wang etal. “Tribology International” Vol. 3, No. 123 (1998) pp. 17-35. Afterirradiation in air the gap in time before annealing is preferably sevendays but at least before any oxygen diffuses into the area of the rodfrom which the implant is made. It has been found that it takes at leastseven days to diffuse through the surface layer.

[0066] Free radicals generated during an irradiation step should bereduced to an acceptable level by annealing before exposure to oxygen.The portion of the material from which the implant is made contains freeradicals and if it is exposed to air or other oxidants after themanufacturing process, oxidation will occur. The bulk portion of thepolymer from which the implant is to be made should be annealed at anelevated temperature while out of contact with oxygen for a prescribedtime. This is because the rate of free radical reactions (reactions 10through 12) increases with increasing temperature, according to thefollowing general expressions: $\begin{matrix}{{\frac{{r}\quad \bullet}{t} = {{{k_{1}\left\lbrack {r\quad \bullet} \right\rbrack}\quad {and}\quad \frac{{P}\quad \bullet}{t}} = {k_{2}\left\lbrack {P\quad \bullet} \right\rbrack}}}\quad} & (13)\end{matrix}$

[0067] Compared to room temperature, an elevated temperature not onlyincreases the reaction rate constants, k₁ and k₂, but also helps freeradicals r. and P. to migrate in the plastic matrix to meet otherneighboring free radicals for cross-linking reactions. In general, thedesired elevated temperature is between room temperature to below themelting point of the polymer. For UHMWPE, this temperature range isbetween about 25° C. and about 140° C. It is to be noted that the higherthe temperature used, the shorter the time period needed to combine freeradicals. Additionally, due to the high viscosity of a UHMWPE melt, theformed UHMWPE often contains residual (internal) stress caused byincomplete relaxation during the cooling process, which is the last stepof the forming process. The annealing process described herein will alsohelp to eliminate or reduce the residual stress. A residual stresscontained in a plastic matrix can cause dimensional instability and isin general undesirable.

[0068] In the preferred embodiment, the sequential irradiation followedby sequential annealing after each irradiation is performed in air on apreform such as an extruded rod, bar or compression molded sheet madefrom polyethylene and preferably UHMWPE. Obviously, the final sequentialannealing must take place prior to the bulk material of the final partor implant being exposed to air. Normally, it takes at least seven daysfor atmospheric oxygen to diffuse through the outer layer ofpolyethylene and deeply enough into rod, bar or sheet to effect the bulkpolyethylene forming the final part. Therefore, the last annealing inthe sequence preferably should take place prior to the time required forthe oxygen to diffuse deeply into the rod. Of course, the more materialwhich must be machined off to reach the finished part, the longer onecan wait for the completion of the sequential irradiation and annealingprocess.

[0069] If the sequential irradiation/annealing process is performed on afinal product, such as an acetabular cup, after machining, the polymericcomponent is preferably packaged in an air tight package in anoxidant-free atmosphere, i.e. less than 1% volume by volume. Thus, allair and moisture must be removed from the package prior to the sealingstep. Machines to accomplish this are commercially available, such asfrom Orics Industries Inc., College Point, N.Y., which flush the packagewith a chosen inert gas, vacuum the container, flush the container forthe second time, and then heat seal the container with a lid. Ingeneral, less than 0.5% (volume by volume) oxygen concentration can beobtained consistently. An example of a suitable oxidant impermeable (airtight) packaging material is polyethylene terephthalate (PET). Otherexamples of oxidant impermeable packaging material is poly(ethylenevinyl alcohol) and aluminum foil, whose oxygen and water vaportransmission rates are essentially zero. All these materials arecommercially available. Several other suitable commercial packagingmaterials utilize a layer structure to form a composite material withsuperior oxygen and moisture barrier properties. An example of this typeis a layered composite comprised of polypropylene/poly (ethylene vinylalcohol) /polypropylene.

[0070] With a final product, following each irradiation step, the heattreatment or annealing step should be performed while the implant is outof contact with oxygen or in an inert atmosphere and at an elevatedtemperature to cause free radicals to form cross-links withoutoxidation. If proper packaging materials and processes are used andoxidant transmission rates are minimal, then the oxidant-free atmospherecan be maintained in the package and a regular oven with air circulationcan be used for heat treatment after sterilization. To absolutely ensurethat no oxidants leak into the package, the oven may be operated under avacuum or purged with an inert gas. In general, if a higher temperatureis used, a shorter time period is required to achieve a prescribed levelof oxidation resistance and cross-linking. In many cases, therelationship between the reaction temperature and the reaction ratefollows the well-known Arrhennius equation:

k₁ or k₂=A * exp (−ΔH/T)  (14)

[0071] where k₁ and k₂ are reaction rate constants from reactions 13 and14

[0072] A is a reaction dependent constant

[0073] ΔH is activation energy of reaction

[0074] T is absolute temperature (K).

[0075] It is very important to ensure that the number of free radicalshas been reduced to a minimal or an accepted level by the heattreatment. This is because the presence of an oxidant causes not onlythe oxidation of pre-existing free radicals, but also the formation ofnew free radicals via reactions 2 through 7. When the number of freeradicals grows, the extent of oxidation and the oxidation rate willincrease according to the following equations: $\begin{matrix}{{\frac{{r}\quad \bullet}{t} = {{{{k_{3}\left\lbrack {r\quad \bullet} \right\rbrack}\left\lbrack O_{2}\quad \right\rbrack}\quad {and}\quad \frac{{P\bullet}}{t}} = {{k_{4}\left\lbrack {P\quad \bullet} \right\rbrack}\left\lbrack O_{2}\quad \right\rbrack}}}\quad} & (15)\end{matrix}$

[0076] Where free radicals r. and P. can grow in number in the presenceof oxidants and in turn increase the oxidation rates. It is also to benoted that the oxidation reaction rate constants k₃ and k₄ increase withincreasing temperature, similar to k₁ and k₂. Therefore, to determine ifa certain level of residual free radicals is acceptable or not, it isrequired to evaluate specific material properties after the plasticsample is stored or aged at the application temperature for a timeperiod which is equal to or longer than the time period intended for theapplication of the plastic component. An alternative to the method toassess the aging effect is to raise the aging temperature of the plasticsample for a shorter time period. This will increase the reaction rateconstants k₃ and k₄ significantly and shorten the aging time. It hasbeen found that an acceptable level of residual free radicals is1.0×10¹⁷/g for UHMWPE use for orthopedic implants.

EXAMPLE I

[0077] As stated above, the ultra-high molecular weight polyethyleneextruded rod is irradiated for a sufficient time for an accumulatedincremental dose of between 2 and 5 (MRads) (20 to 50 kGy). After thisirradiation step, the extruded rod is annealed in air preferably at atemperature below its melting point, preferably at less than 135° C. andmore preferably between 110° C. and 130° C. The irradiation andannealing steps are then repeated two or more times so that the totalradiation dose is between 4 and 15 MRads (50 to 150 kGy). In thisexample, the rod is irradiated for a total dose of 3 MRad and thenannealed at 130° C. for 24 hours, allowed to cool to room temperatureand sit for 3 days and then reirradiated for a dose of 3.0 MRads (atotal dose of 6 MRads) again annealed at 130° C. for 24 hours, allowedto cool at room temperature and sit for an additional 3 days and thenirradiated a third time with a 3.0 MRad dose (for a total of 9 MRads)and again annealed at 130° C. for 24 hours. The rod is cooled to roomtemperature and is then moved into the manufacturing process which formsthe orthopedic implant by machining.

[0078] The above example can also be applied to compression molded sheetwith, for example, a tibial component being manufactured out of thesequentially irradiated and annealed material.

[0079] In the preferred embodiment, the total radiation dose can beanywhere between 5 and 15 MRads and most preferably 9 MRads applied inthree doses of 3 MRads, as done in the above example. The length of timebetween sequential irradiation is preferably between 3 to 7 days. Whilethe annealing step is preferably performed after the irradiation step,it is possible to heat the rod to the annealing temperatures andirradiate it sequentially in the heated state. The rod may be allowed tocool between doses or can be maintained at the elevated temperatures forthe entire series of doses.

EXAMPLE II

[0080] A machined tibial implant in its final form is packaged in anoxygen reduced atmosphere having an oxygen concentration less than 1%volume by volume. The packaged implant is then processed as described inExample I through a series of three (3) irradiation and annealing cyclesas described above with the total radiation dose being 9 MRads. Theimplant was then boxed and ready for final shipping and use.

EXAMPLE III

[0081] Two ultra-high molecular weight polyethylene rods (one ofcompression molded GUR 1020 and the other of ram extruded GUR 1050) witha cross-section profile of 2.5-inch×3.5-inch (GUR 1020) and 3.5-inchdiameter (GUR 1050), respectively, were used. Lengths of these rods weresectioned into 18-inch lengths; three 18-inch rods (staggered andseparated by small paper boxes) were packaged in a paper carton beforethe sequential radiation process. The purpose of the packaging andstaggering was to reduce the possibility of blocking the radiation(gamma rays) to each individual rod during the process.

[0082] The rods went through the following sequential process in air:

[0083] 1. Each rod received a nominal dose of 30 kGy gamma radiation;

[0084] 2. Each was then annealed at 130° C. for 8 hours; and

[0085] 3. Steps 1 and 2 were repeated two more times. Preferably, therepeated steps occurred within three days each.

[0086] While the process was done in air, it could be performed in aninert atmosphere such as nitrogen.

[0087] The rods received a nominal 90 kGy total dosage of gammaradiation after the completion of the above sequential process. The GUR1020 rod is designated as sample “A” and the GUR 1050 rod as sample “B”.When done in air, 2 mm of the entire outer surface of each rod isremoved after the entire process is complete.

[0088] Control—The following materials/process had been selected as“Control”:

[0089] 1. The conventionally (in nitrogen or vacuum N₂VAC) processedmolded GUR 1020 and extruded GUR 1050 rods received in a single dose 30kGy gamma radiation sterilization in nitrogen but no annealing and weredesignated samples “C” and “D,” respectively.

[0090] 2. A GUR 1050 rod that received 90 kGy total dose(non-sequentially) followed by annealing at 130° C. for 8 hours and wasdesignated as sample “E”.

[0091] Tensile Test—The ASTM D 638 Type IV specimens were used for thetensile property evaluation of samples A-E. Tensile properties weredetermined from the average of six (6) specimens. An Instron Model 4505Test System was used to conduct this evaluation. Crosshead speed was 5.0mm/min. The results are listed in Table I.

[0092] Free Radical Concentration Measurement—All free radicalmeasurement was conducted before the accelerated aging treatment. Thespecimens are 3 mm diameter, 10 mm long cylinders. This evaluation wascarried out at the University of Memphis (Physics Department). Freeradical concentration was measured and calculated from average of three(3) specimens. Free radical measurements were performed using electronspin resonance technique. This is the only technique that can directlydetect free radicals in solid and aqueous media. An ESR spectrometer(Bruker EMX) was used in this evaluation.

[0093] Oxidation Resistance Measurement—Oxidation index/profilemeasurement was performed after accelerated aging using the protocol perASTM F 2003 (5 atm O2 pressure at 70° C. for 14 days) on specimensmachined into 90×20×10 mm thick rectangular blocks from the center ofthe rods. The oxidation analysis was performed on a Nicolet model 750Magna-IR™ spectrometer per ASTM F2102-01 using an aperture 100 μm×100 μmand 256 scans. An oxidation index was defined by the ratio of thecarbonyl peak area (1660 to 1790 cm⁻¹) to the 1370 cm⁻¹ peak area (1330to 1390 cm⁻¹). A through-the-thickness (10 mm) oxidation index profileis generated from an average of three (3) specimens. The 0 and 10 mmdepths represent upper and lower surfaces of specimens. The maximumoxidation index of each specimen was used to determine if there was asignificant difference.

[0094] Statistical Analysis—Student's t Test—Test of Significance—Astudent's t test (two-tail, unpaired) was conducted to measurestatistical significance at the 95% confidence level (p<0.05).

[0095] Tensile Test Results TABLE 1 Comparison Of Tensile Properties, N= 6 Yield Ultimate Strength Strength Elongation at Sample Material (MPa)(MPa) Break (%) A GUR 1020 24.9 ± 0.6 59.3 ± 1.5 301 ± 7 B GUR 1050 25.6± 0.4 54.8 ± 1.2 255 ± 7 C GUR 1020 25.2 ± 0.1 57.0 ± 2.3  372 ± 10 DGUR 1050 24.5 ± 0.2 56.4 ± 4.0  370 ± 10 E GUR 1050 23.9 ± 0.4 51.0 ±2.1 214 ± 5

[0096] The sequential process of samples “A” and “B” maintains bothtensile yield and ultimate strength (when compared to their respectivecounterparts samples C and D). Consequently, the null hypothesis thatsequential process maintains (p=0.001) tensile strengths was verified.Results also indicated that a sequential process improved elongation atbreak in radiation-crosslinked GUR 1050 by 19% (p=0.001) over a processthat produced crosslinking by a single-dose delivery of 90 kGy(non-sequentially) and annealed at 130° C. for 8 hours (sample E).

[0097] The sequential crosslinking reduces free radical concentration inradiation-crosslinked GUR 1020 and 1050 by 87% (p=0.001) and 94%(p=0.001), respectively when comparing to their respective N2VAC™process counterparts, samples C and D. The sequential crosslinkingprocess also reduces free radical concentration in radiation-crosslinkedGUR 1050 by 82% (p=0.001) over a process that produced crosslinking by asingle-dose delivery of 90 kGy (non-sequentially) and annealed at 130°C. for 8 hours (sample E).

[0098] The sequential crosslinking process reduces the maximum oxidationindex in radiation crosslinked GUR 1020 and 1050 by 82% (p=0.001) and86% (p=0.001), respectively (when compared to control samples C and D).The process also reduces the maximum oxidation index inradiation-crosslinked GUR 1050 by 74% (p=0.001) over a process thatproduced crosslinking by a single-dose delivery of 90 kGy(non-sequentially) and annealed at 130° C. for at least 8 hours (sampleE). The sequential irradiation and annealing process maintains theoriginal tensile yield and ultimate strengths reduces free radicalconcentration and improves oxidation resistance. It is believed thatsequential cross-linking is a gentler process than a single doseprocess.

[0099] Furthermore, this process has significant benefits over asingle-dose delivery of 90 kGy (non-sequentially) and annealed at 130°C. for 8 hours in at least three areas. First there is a lower freeradical concentration, second a better oxidation resistance and third abetter tensile elongation.

[0100] While the preferred process is three sequential applications of30 kGy each followed by annealing at 130° C. for eight (8) hours, a twostep process of 30 kGy to 45 kGy radiation applied twice, each followedby an annealing at about 130° C. for about 8 hours may be used.

[0101] If it is desired to have an additional sterilization step afterthe sequential irradiation and annealing of the ultra-high molecularweight polyethylene preformed part or packaged final part then the partmay be sterilized via non-irradiative methods such as ethylene oxide orgas plasma and then packaged or repackaged and shipped in the standardmanner.

EXAMPLE IV Effect of Sequential Cross-Link Dose on the PhysicalProperties of UHMWPE

[0102] Materials and Methods—Medical-grade UHMWPE extruded bars (GUR1050, Perplas Medical), with a weight average molecular weight of 5×10⁶Daltons and a diameter of 83 mm were used for all subsequent treatments.The GUR 1050 bars had a total original length of 5 meters and wereextruded from the same polymer and extrusion lots. These bars were cutinto 460 mm long sections and irradiated with gamma ray at roomtemperature in ambient air.

[0103] The treatments of these materials are listed in Table 3. Theterminologies 1X means a single cycle of irradiation and annealing and2X and 3X denote that the materials received the sequential cross-linkprocess, two and three times, respectively; these materials received anominal dose of 3.0 MRads during each step of radiation. Annealing wasdone at 130° C. for 8 hours after each radiation dose.

[0104] Differential Scanning Calorimetry (DSC)—DSC samples were cut frommachined 1 mm thick sheets. Specimens (˜4 mg) were heated from 50° C. atheating rate of 10 C./min in a Perkin-Elmer DSC 7 to 175°C. The meltingtemperature was determined from the peak of the melting endotherm. Theheat of fusion was calculated through an integration of the area underthe melting endotherm between 60° C. and 145° C. Crystallinity wascalculated using the abovementioned heat of fusion divided by 288 J/g,the heat of fusion of an ideal polyethylene crystal.

[0105] Results and Discussion—The measured melting temperature andcrystallinity are listed in Table 2. After the three consecutivesequential cross-link process; materials received 3.0, 6.0 and 9.0 MRadstotal gamma-radiation showed no change in crystallinity when comparingto material that received a 3.0 MRads gamma-radiation in a containerwith less than 0.5% oxygen (58% v 57.6%) while remelting caused asignificant decrease in crystallinity from 57% to 48%. TABLE 2 MeltingTemperature, Crystallinity, Treatment ° C. % No Radiation 135.8 ± 0.154.3 ± 0.7 3.0 MRads single dose in a 139.9 ± 0.2 57.6 ± 0.8 Containerwith less than 0.5% oxygen 1X cross-linked and 140.1 ± 0.2 56.7 ± 0.9annealed one time, 3.0 MRads 2X sequentially cross-link 141.1 ± 0.1 57.4± 0.6 and annealed, 6.0 MRads 3X sequentially cross-link 142.3 ± 0.158.0 ± 0.9 and annealed, 9.0 MRads 5 MRads single dose 137.0 ± 0.2 48.2± 0.7 cross-link, remelted at 150° C. for 8 hours 10 MRads single dose139.7 ± 0.2 48.6 ± 0.6 cross-link, remelted at 150° C. for 8 hours

EXAMPLE V Effect of Sequential Cross-link Dose on the Tensile Propertiesof UHMWPE

[0106] Materials and Methods—The materials for tensile propertyevaluation are the same as the physical property materials described inExample IV above. Six tensile specimens were machined out of the centerof the 83 mm diameter bars according to ASTM F648, Type IV and 1 mmthick. Tensile property evaluation was carried out on anelectromechanical Instron model 4505 universal test frame at a speed of50 mm/inch. The treatments of these materials are listed in Table 2.

[0107] Results and Discussion—The tensile properties (yield strength,ultimate strength and elongation at break) are illustrated in Table 3.The sequential cross-link process increased tensile yield strengthfollowing each treatment. This process also maintained ultimate tensilestrength in a cross-link UHMWPE while remelt processes significantlydecreased both yield and ultimate strengths when comparing to samplesthat received a 3.0 MRads gamma-radiation in a container with less than0.5% oxygen. TABLE 3 Yield Strength Ultimate Elongation at Treatment(MPa) Strength (MPa) Break (%) No radiation 21.4 ± 0.5 52.2 ± 3.1 380 ±18 3.0 MRads single 24.5 ± 0.2 54.6 ± 4.0 356 ± 14 dose in a containerwith less than 0.5% oxygen 1x cross-link and 22.7 ± 0.2 50.4 ± 2.8 338 ±10 annealed, a single time 3.0 MRads 2X sequentially 23.5 ± 0.5 52.2 ±3.9 299 ± 11 cross-link and annealed, 6.0 MRads total dose 3Xsequentially 25.6 ± 0.4 54.8 ± 1.2 255 ± 7  cross-link and annealed, 9.0MRads total dose 5 MRads single dose 21.3 ± 0.3 48.2 ± 3.1 297 ± 8 cross-link, remelted at 150° C. for 8 hours 10 MRads single 21.6 ± 0.443.6 ± 0.7 260 ± 12 dose cross-link remelted at 150° C. for 8 hours

EXAMPLE VI Effect of Sequential Cross-link Dose on the Wear Propertiesof UHMWPE Acetabular Cups

[0108] Materials and Methods—Two types of UHMWPE materials, ram extrudedGUR 1050 bars (83 mm diameter) and compression molded GUR 1020 sheets(51 mm×76 mm cross-section were treated). The sequential cross-linkprocess was performed on the GUR 1050 materials either 2 or 3 times andon GUR 1020 material 3 times only. The nominal radiation dose for eachradiation/annealing cycle was 3.0 MRads. A current standard product,Trident™ design 32 mm acetabular cup (manufactured by HowmedicaOsteonics Corp. from GUR 1050 bar stock) sterilized under a 3.0 MRadsgamma-radiation in a container with less than 0.5% oxygen, was used as areference material.

[0109] All acetabular cups were fabricated according to prints for theTrident™ design 32 mm insert (Howmedica Osteonics Corp. Cat. No.620-0-32E). The standard cobalt chrome femoral heads (6260-5-132) wereobtained, these femoral heads were of matching diameter to the insertinside diameter of 32 mm.

[0110] An MTS 8-station hip simulator was used to perform the wear test.The cups were inserted into metal shells as in vivo. The shells werethen secured into polyethylene holders that were in turn fitted ontostainless steel spigots. Each head was mounted onto a stainless steeltaper that was part of a reservoir containing a fluid serum media. Theserum reservoir was mounted on a 23-degree inclined block. A standardphysiological cyclic load between two peak loads of 0.64 and 2.5 kN at 1Hz was applied to all cups. This cyclic load was applied through thecentral axes of the cup, head and block.

[0111] The serum used for this test was a fetal-substitute alpha calffraction serum (ACFS) diluted to a physiologically relevant value ofabout 20 grams per liter of total protein. A preservative (EDTA) about0.1 vol. % was added to minimize bacteria degradation. Each reservoircontained about 450 milliliters of abovementioned ACFS with EDTA. Thisfluid in the reservoir was replaced with fresh ACSS with EDTA every250,000 cycles. During the fluid replacement process, the samples wereremoved from the machine, cleaned and weighed.

[0112] Results and Discussion—The wear rate of each treatment isillustrated in Table 4; the measurement unit given is cubic millimetersper million cycles (mm³/mc). The wear rate was corrected for the effectof fluid absorption. The cups subject to the 2X and 3X sequentialcross-link processes significantly reduced wear rate in UHMWPEacetabular cups by 86 to 96% when comparing to cups that received a 3.0MRads gamma-radiation in a container with less than 0.5% oxygen. TABLE 4Wear Rate Reduction in Wear Treatment (mm³/mc) Rate (%) GUR 1050received 3.0 MRads 37.6 NA in a container with less than 0.5% oxygen (areference material) GUR 1050 received 2X 5.3 86 sequentially cross-linkand annealed, 6.0 MRads total GUR 1050 received 3X 1.4 96 sequentiallycross-link and annealed, 9.0 MRads total GUR 1020 received 3X 2.5 93sequentially cross-link and annealed, 9.0 MRads

EXAMPLE VII Effect of Sequential Cross-link Dose on the Free RadicalConcentration in UHMWPE

[0113] Materials and Methods—The materials for free radicalconcentration evaluated were:

[0114] 1. GUR 1050 that received 3.0 MRads in a container with less than0.5% oxygen (A reference material).

[0115] 2. GUR 1050 that received 2X (6.0 MRads) sequentially cross-linkand annealed.

[0116] 3. GUR 1050 that received 3X (9.0 MRads) sequentially cross-linkand annealed.

[0117] 4. GUR 1050 that received a 9.0 MRads single total dose ofcross-link radiation and annealed at 130° C. for 8 hours.

[0118] The specimens are 3 mm diameter, 10 mm long cylinders fabricatedfrom abovementioned components. This evaluation was carried out at theUniversity of Memphis (Physics Department, Memphis, Tenn.). Free radicalconcentration was measured and calculated from an average of three (3)specimens. Free radical measurements were performed using electron spinresonance technique. This is the only technique that can directly detectfree radicals in solid and aqueous media. A top-of-the-line ESRspectrometer (Bruker EMX) was used in this evaluation.

[0119] Results and Discussion—The free radical concentration in thematerials is illustrated in Table 5; the measurement unit given is spinsper grams (spins/g). The materials subjected to the 2X and 3X sequentialcross-link processes showed a significant reduction in free radicalconcentration about 94 to 98% when comparing to a GUR 1050 material thatreceived a 3.0 MRads gamma-radiation in a container with less than 0.5%oxygen. The materials subjected to the 2X and 3X sequential cross-linkprocesses also showed a significant reduction in free radicalconcentration about 82 to 92% when comparing to a GUR 1050 material thatreceived a 9.0 MRads total dose of gamma-radiation and annealed at 130°C. for 8 hours. TABLE 5 Free Radical Concentration Reduction in Free(10E + 14 Radical Treatment spins/g) Concentration (%) GUR 1050 received3.0 MRads 204 ± 14 NA in a container with less than 0.5% oxygen (areference material) GUR 1050 received 2X  5 ± 1 98 sequentiallycross-link and annealed, 6.0 MRads GUR 1050 received 3x 12 ± 1 94sequentially cross-link and annealed, 9.0 MRads GUR 1050 received 9.0MRads 67 ± 4 67 cross-link and annealed 130° C. for 8 hours

EXAMPLE VIII Effect of Sequential Cross-link Dose on the OxidationResistance Property of UHMWPE

[0120] Materials and Methods—The materials for oxidation resistanceevaluation were:

[0121] 1. GUR 1050 that received 3.0 MRads in a container with less than0.5% oxygen (A reference material).

[0122] 2. GUR 1050 that received 3X (9.0 MRads) sequentially cross-linkand annealed.

[0123] 3. GUR 1050 that received a 9.0 MRads single total dose ofcross-link radiation and annealed at 130° for 8 hours.

[0124] An accelerated aging protocol per ASTM F 2003 (5 atm oxygenpressure at 70° C. for 14 days) was carried out at Exponent FailureAnalysis Associates (Philadelphia, Pa.). The specimens were machined90×20×10 mm rectangular blocks. The oxidation analysis was performed ona Nicolet model 750 Magna-IR™ spectrometer per ASTM F2102-01 using anaperture 100 μm×100 μm and 256 scans. An oxidation index was defined bythe ratio of the carbonyl peak area (1660 to 1790 cm⁻¹) to the 1370 cm⁻¹peak area (1330 to 1390 cm⁻¹). A through-the-thickness (10 mm) oxidationindex profile was generated from an average of three (3) specimens. The0 and 10 mm depths represented surfaces of specimens. The maximumoxidation index of each specimen was used to determine if there was asignificant difference.

[0125] Results and Discussion—Oxidation index profiles and the maximumoxidation index are illustrated in FIG. 1 and Table 6, respectively. TheGUR 1050 materials subjected to the 3X sequential cross-link processshowed a significant reduction in both an oxidation index profile andmaximum oxidation index. The sequential cross-link process significantlyreduced the maximum oxidation index in 3X GUR 1050 by 86% when comparingto a GUR 1050 material that received a 3.0 MRads gamma-radiation in acontainer with less than 0.5% oxygen. The GUR 1050 materials subjectedto the 3X sequential cross-link process also showed a significantreduction in maximum oxidation index by 72% when comparing to a GUR 1050material that received a 9.0 MRads total dose of gamma-radiation andannealed at 130° C. for 8 hours. TABLE 6 Treatment Maximum OxidationIndex GUR 1050 received 3.0 MRads in a 2.60 ± 0.02 container with lessthan 0.5% oxygen (a reference material) GUR 1050 received 3Xsequentially 0.36 ± 0.02 cross-link and annealed, 9.0 MRads GUR 1050received 9.0 MRads cross-link 1.29 ± 0.03 and annealed 130° C. for 8hours

EXAMPLE IX Effect of Sequential Cross-link Dose on the Wear Propertiesof Direct Compression Molded UHMWPE Tibial Inserts

[0126] Materials and Methods—All direct compression molded (DCM) andmachined Howmedica Osteonics Corp. Scorpio® PS tibial inserts werefabricated from GUR 1020 UHMWPE. DCM Scorpio® PS direct molded tibialinserts were treated with the sequential cross-link process (radiationand annealing) two times (2X), a nominal dose of 4.5 MRads during eachstep of radiation. The total accumulation of gamma-radiation in thesecomponents was 9.0 MRads. These components were packaged in an airimpermeable pouch with less than 0.5% oxygen. Scorpio® PS tibial inserts(Howmedica Osteonics Corp. Cat. No. 72-3-0708) were machined fromcompression molded GUR 1020 material and obtained from an in-houseorder. These components then received gamma-radiation sterilization at anominal dose of 3.0 MRads in a container with less than 0.5% oxygen.Wear test was performed on an MTS knee simulator according to an ISOstandard 14243 Part 3.

[0127] Results and Discussion—The wear test results are illustrated inTable 7; the measurement unit given is cubic millimeters per millioncycles (mm³/mc) . The wear rate was corrected for the effect of fluidabsorption. The DCM Scorpio® PS tibial inserts subjected to the 2X (4.5MRad) sequential cross-link process significantly reduced wear rate inUHMWPE tibial inserts by 88% when comparing to Scorpio® PS tibialinserts that received a 3.0 MRads gamma-radiation in a container withless than 0.5% oxygen. TABLE 7 Wear Rate Reduction in Wear Treatment(mm³/mc) Rate (%) Scorpio ® PS machined from 32.6 ± 6.8  NA compressionmolded GUR 1020, received 3.0 MRads in a container with less than 0.5%oxygen (a reference material) DCM Scorpio ® PS GUR 1020 3.8 ± 0.1 88received 2X (4.5 MRads) sequentially cross-link and annealed, 9.0 MRadstotal

EXAMPLE X Effect of Sequential Cross-link Dose on the Free RadicalConcentration in Direct Compression Molded UHMWPE Tibial Inserts

[0128] Materials and Methods—The materials for free radicalconcentration evaluation are the same as the wear test materialsdescribed in Example IX, above. The specimens are 3 mm diameter, 10 mmlong cylinders fabricated from abovementioned components. Thisevaluation was carried out at the University of Memphis (PhysicsDepartment, Memphis, Tenn.). Free radical concentration was measured andcalculated from an average of three (3) specimens. Free radicalmeasurements were performed using electron spin resonance technique.This is the only technique that can directly detect free radials insolid and aqueous media. A top-of-the-line ESR spectrometer (Bruker EMX)was used in this evaluation.

[0129] Results and Discussion—The free radical concentration in thematerials is illustrated in Table 8; the measurement unit given is spinsper gram (spins/g). The DCM Scorpio® PS tibial inserts subjected to the2X (4.5 MRads) sequential cross-link processes showed a significantreduction in free radical concentration of 97% when comparing to aScorpio® PS machined from compression molded GUR 1020 that received a3.0 MRads of gamma-radiation sterilization in a container with less than0.5% oxygen. TABLE 8 Free Radical Concentration Reduction in Free (10E +14 Radical Treatment spins/g) Concentration (%) Scorpio ® PS machinedfrom 325 ± 28 NA compression molded GUR 1020, received 3.0 MRads in acontainer with less than 0.5% oxygen (a reference material) DCMScorpio ® PS GUR 1020  9 ± 0 97 received 2X (4.5 MRads) sequentiallycross-link and annealed, 9.0 MRads total

EXAMPLE XI Effect of Sequential Cross-link Dose on the OxidationResistance of Direct Compression Molded UHMWPE Tibial Inserts

[0130] Materials and Methods—The materials for oxidation resistanceevaluation are the same as the wear test materials described in ExampleIX, above. An accelerated aging protocol per ASTM F 2003 (5 atm oxygenpressure at 70° C. for 14 days) was carried out at Howmedica Osteonics(Mahwah, N.J.). The specimens were machined and sequentially cross-link2X (4.5 MRads) DCM Scorpio® PS tibial inserts. The oxidation analysiswas performed on a Nicolet model 750 Magna-IR™ spectrometer per ASTMF2102-01 using an aperture 100 μm×100 μm and 256 scans. An oxidationindex was defined by the ratio of the carbonyl peak area (1660 to 1790cm⁻¹) to the 1370 cm⁻¹ peak area (1330 to 1390 cm⁻¹). Athrough-the-thickness (about 6 mm) oxidation index profile was generatedfrom an average of three (3) specimens. The 0 and 6 mm depthsrepresented articulating and back surfaces of specimens. The maximumoxidation index of each specimen was used to determine if there was asignificant difference.

[0131] Results and Discussion—Oxidation index profiles and the maximumoxidation index are illustrated in FIG. 2 and Table 9, respectively. TheDCM Scorpio® PS tibial inserts subjected to the 2X (4.5 MRads)sequential cross-link processes showed a significant reduction in anoxidation index profile and maximum oxidation index. The sequentialcross-link process reduced the maximum oxidation index in 2X (4.5 MRads)DCM GUR 1020 Scorpio® PS tibial inserts by 90% when comparing to aScorpio® PS machined from compression molded GUR 1020 that received a3.0 MRads of gamma-radiation sterilization in a container with less than0.5% oxygen. TABLE 9 Treatment Maximum Oxidation Index Scorpio ® PSmachined from compression 0.30 ± 0.02 molded GUR 1020, received 3.0MRads in a container with less than 0.5% oxygen (a reference material)GUR 1020 received 2X (4.5 MRads) 3.10 ± 0.03 sequentially cross-link andannealed, 9.0 MRads total

[0132] Although the invention herein has been described with referenceto particular embodiments, it is to be understood that these embodimentsare merely illustrative of the principles and applications of thepresent invention. It is therefore to be understood that numerousmodifications may be made to the illustrative embodiments and that otherarrangements may be devised without departing from the spirit and scopeof the present invention as defined by the appended claims.

1. A preformed material for subsequent production of a medical implantwith improved wear resistance comprising a polyethylene cross-linked atleast twice by irradiation and thermally treated by annealing after eachirradiation.
 2. The preformed material as set forth in claim 1, whereinthe material is cross-linked by a total radiation dose from about 2 toabout 100 MRad.
 3. The preformed material as set forth in claim 2,wherein the total radiation dose is between about 5 to about 10 MRad. 4.The preformed material as set forth in claim 3, wherein three radiationdoses are applied with an incremental dose for each irradiation isbetween about 2 and about 5 MRad.
 5. The preformed material as set forthin claim 1, wherein three radiation doses are applied with anincremental dose for each irradiation being between about 2 and about 5MRad.
 6. The preformed material as set forth in claim 5, wherein thetotal radiation dose is between about 5 to about 10 MRad.
 7. Theorthopedic preformed material as set forth in claim 1, wherein thepolyethylene has a weight average molecular weight of greater than400,000.
 8. The preformed material as set forth in claim 1, wherein theannealing takes place in air at a temperature greater than 25° C.
 9. Thepreformed material as set forth in claim 8, wherein the annealing takesplace for a time and temperature selected to be at least equivalent toheating said irradiated material at 50° C. for 144 hours as defined byArrhennius equation (14).
 10. The preformed material as set forth inclaim 9, wherein said material is heated for at least about four hours.11. The orthopedic preformed material as set forth in claim 1, whereinthe polyethylene is at room temperature for each irradiation.
 12. Thepreformed material as set forth in claim 1, wherein the polyethylene iscross-linked three times by irradiation and thermally treated byannealing after each irradiation at a temperature between 25° C. and135° C. for at least 4 hours.
 13. A method for increasing the wearresistance of a preformed polyethylene comprising: irradiating thepreformed polyethylene in the solid state at least two times; andannealing the preformed polyethylene after each irradiation.
 14. Themethod for increasing the wear resistance as set forth in claim 13,wherein the material is cross-linked by a total radiation dose fromabout 1 to about 100 MRad.
 15. The method for increasing the wearresistance as set forth in claim 14, wherein the total radiation dose isbetween about 5 to about 10 MRad.
 16. The method for increasing the wearresistance as set forth in claim 15, wherein an incremental dose foreach irradiation is between about 2 and about 5 MRad.
 17. The method forincreasing the wear resistance as set forth in claim 16, wherein anincremental dose for each irradiation is between about 2 and about 5MRad.
 18. The method for increasing the wear resistance as set forth inclaim 17, wherein the total radiation dose is between about 4 to about10.5 MRad.
 19. The method for increasing the wear resistance as setforth in claim 18, wherein the weight average molecular weight of thepolyethylene is greater than 400,000.
 20. The method for increasing thewear resistance as set forth in claim 19, wherein the annealing takesplace at a temperature greater than 25° C.
 21. The method as set forthin claim 29 wherein the annealing takes place between 110° C. and 135°C.
 22. The method for increasing the wear resistance as set forth inclaim 20, wherein the annealing takes place for a time and temperatureselected to be at least equivalent to heating said irradiated materialat 50° C. for 144 hours as defined by Arrhennius equation (14).
 23. Themethod for increasing the wear resistance as set forth in claim 23,wherein said material is heated for at least about 4 hours.
 24. Themethod as set forth in claim 13 further including the step of machiningthe preformed polyethylene into a medical implant.
 25. The method as setforth in claim 13, wherein the material polyethylene is cross-linkedthree times by irradiation and thermally treated by annealing after eachirradiation at a temperature between 25° C. and 135° C. for at leastabout 4 hours.
 26. A medical device comprising a polyethylene materialirradiated at least two times and annealed at a temperature lower thanthe melting point of the material after each irradiation.